相关实验视频

Updated: Jun 16, 2025

Expression, Solubilization, and Purification of Eukaryotic Borate Transporters

Expression, Solubilization, and Purification of Eukaryotic Borate Transporters

Published on: March 7, 2019

人类酸盐输送器1的运输和基质选择的结构基础

Jingjing He¹, Guoyun Liu¹, Fang Kong²

¹Department of Cardiology, First Affiliated Hospital of USTC, MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.

|August 15, 2024

概括

对URAT1的结构洞察力,它是酸盐吸收的关键载体,揭示了其传输机制. 这项研究为通过了解尿酸识别来开发更具体的抗痛风药物提供了基础.

科学领域:

生物化学生物化学
结构生物学结构生物学
腎臟病學 (nephrology) 是一種醫學專業.

背景情况:

高血清尿酸盐水平是痛风的主要危险因素.
URAT1 是脏的关键尿酸运输体,也是抗高尿素血症药物的标.
目前的URAT1药物由于特异性和副作用较低而存在局限性,阻碍了临床使用.

研究的目的:

阐明URAT1功能和酸盐运输的结构基础.
为开发新型抗痛风疗法提供结构性信息.
了解URAT1及其同类OAT4.4的机制.

主要方法:

使用冷电子显微镜 (cryo-EM) 确定了人类URAT1的结构 (R477S),其与尿酸盐的复合物,以及OAT4.
进行结构比较以分析域移动和构造变化.
生物化学分析确定了涉及载体抑制的关键残留物.

主要成果:

冷-EM结构显示,URAT1 (R477S) 和OAT4采用主要促进者超级家族 (MFS) 折叠,分别具有向外和向内开放的状态.
一个保存的氨酸残留物 (URAT1-Arg477) 被确定为化物介导抑制的关键.
酸1 ((R477S) -酸复合结构阐明了酸的特定识别机制.

结论:

这项研究揭示了URAT1通过域旋转的交替访问传输机制.
结构数据澄清了尿酸识别的特异性,这对于有针对性的药物设计至关重要.
这项工作促进了对URAT1功能的理解,为改善痛风治疗铺平了道路.

关键词:

科普:分子生物学分子生物学在 OAT4AT4 中使用.乌拉特1是URAC1的产品之一.低温电磁波冷却器 (Cryo-EM) 是一个非常好的方法.酸转运器的输送器

更多相关视频

Author Spotlight: Expression and Purification of Human Solute Carrier Transporters Using Codon-Optimized Genes

Author Spotlight: Expression and Purification of Human Solute Carrier Transporters Using Codon-Optimized Genes

Published on: September 29, 2023

Selection of Transporter-Targeted Inhibitory Nanobodies by Solid-Supported-Membrane SSM-Based Electrophysiology

Selection of Transporter-Targeted Inhibitory Nanobodies by Solid-Supported-Membrane SSM-Based Electrophysiology

Published on: May 3, 2021

相关概念视频

The Significance of Membrane Transport

The Significance of Membrane Transport

The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...

Secondary Active Transport

Secondary Active Transport

One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...

Carrier-Mediated Transport

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...

Glucose Transporters

Glucose Transporters

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:

Membrane Transporters

Membrane Transporters

Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...

Facilitated Diffusion

Facilitated Diffusion

The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...